Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene

Abstract

In the light of this confirmatory study, we recommend the systematic analysis of WFS1 gene sequences in patients with parentally inherited diabetes mellitus and deafness (+/- optic atrophy), in particular when diabetogenic mtDNA mutations have been excluded.

Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome

“…Giuliano et al noted an atypical phenotype in a patient whose WFS1 coding region had only one mutation identified (14). In addition, a rare form of autosomal dominant transmission of diabetes mellitus, deafness, optic atrophy, and no other manifestations of Wolfram disease was associated with the E864K mutation in two families (28,29). Thus, the location of WFS1 mutations also seems important to determine the severity of disease.…”

Clinical utility gene card for: Wolfram syndrome

“…This is an autosomal dominant disorder caused by heterozygous variants in WFS1, resulting in sensorineural hearing loss, DM, psychiatric illness and variable optic atrophy within the first decade of life. 10,11 1.6 Analytical methods Bi-directional fluorescent Sanger sequencing of coding and intronexon boundaries of WFS1 is the mainstay analytical method as an initial analysis. CISD2 screening can be performed if WFS2 is suspected, as this is rare.…”

“…18 However, due to the variable order and age of onset of different clinical features, care has to be taken with the interpretation of heterozygous variants in WFS1, which cause Wolfram-like syndrome disorders, including missense mutations associated with autosomal dominant OA and sensorineural hearing loss, 10,19 autosomal dominant nonsyndromic adult-onset diabetes, 20 psychiatric symptoms and autosomal dominant low-frequency nonsyndromic sensorineural hearing loss. 21 In a systematic review, analysing the published clinical data in 392 patients with WFS, 98.2% had DM and 82.14% developed OA.…”

Clinical report: variable phenotypic expression in a large sibling cohort with a deletion of 4p16.1

“…Mutations in WFS1 are also associated with autosomal dominant optic atrophy with hearing impairment 2 and in autosomal dominant low‐frequency sensorineural hearing impairment (LFSNHI) 3, 4. Mutations in WFS1 are also found in patients with diabetes mellitus and hearing impairment 5, in a single family with autosomal dominant optic neuropathy, deafness, and no glucose intolerance 6, and in eight families with autosomal dominant isolated optic atrophy and hearing loss 7.…”

“…Wolfram‐like syndrome is characterized by congenital progressive hearing impairment, diabetes mellitus, and optic atrophy 8. Previous clinical reports of patients with Wolfram‐like syndrome have included several reported families with novel missense mutations in WFS1 and progressive hearing loss, while frequency of reports of optic atrophy and impaired glucose regulation vary 2, 5, 6. The association of Wolfram‐like syndrome and psychiatric diagnoses, including bipolar disorder, schizophrenia, and depression is a point of discussion 1, 7.…”